The organ systems of drinking alcoholics continually sustain damage. In most of these cases, physiologic compensations occur and the organ appears to be functioning normally. However, when the individual suffers additional trauma such as a high fever brought on by an infectious disease, poisoning or injury in an automobile accident, then the reduced tolerance and recouperative capacity become obvious. The alcoholics would suffer more than the normal subject. Very often the accumulated damage from alcoholism combines with a normally survivable insult to become life-threatening. Using the kidney of alcohol-ingesting rats, we studied the effects of chronic alcoholism on such tolerance and recouperative capacity. Preliminary evidence suggests that rats fed with a liquid, alcohol-containing diet for five weeks had normal renal function. However, when such animals were exposed to short term ischemia or a nephrotoxin, their kidneys were much more damaged than those of control rats. Through this multi-disciplinary study involving a nephrologist, a biophysicist, a biochemist and a patholgist, we will examine the following hypothesis: "The kidney cell membrane is affected through chronic alcoholism and thus, when the kidney is exposed to ischemia or nephrotoxins, it will be more susceptible to physical or chemical trauma." We will also study the pharmacologic means to protect the kidney of alcoholics. We will test the effects of membrane-acting drugs such as beta-blockers, calcium entry blockers and, prostaglandin oligomers to examine whether or not these drugs can protect this organ of alcoholic animals against trauma. The success of this project will not only help develop pharmacological means to prevent acute renal failure in alcoholic victims, but also provide a new insight to the devastating effects of alcoholism. It is also expected to help develop general therapeutic means to reduce morbidity and mortality associated with chronic alcohol abuse.